Antineoplastics

Question 1

Elspar

Kidrolase

Answer 1

G1 specific
MOA: deprives cancer cells of asparagine –> cell death
PK: IM inj w no CNS penetration
ADEs: hypersensitivity, high TGs, high BG, clotting abnormalities, immune suppression
Other: used in lymphomas and leukemias

• *can be formulated with PEG tag: pegaspargase
• lower hypersensitivity risk, longer half-life

Question 2

Azathioprine (6-MP)

Answer 2

S phase specific
MOA: incorporated into DNA –> breaks & mismatches
PK: must be activated by HGPRT; low BA (even lower with food); short half-life
ADEs: Myelosuppression, hepatoxicity
DI: allopurinol (XO inhibitor)

Question 3

Cytarabine

Answer 3

S phase specific
MOA: inhibits DNA polymerase
PK: IV only, short half-life
ADEs: pulmonary infiltrates, hepatic enzyme induction, GI issues, myelosuppression
Other: used in AML; no activity in solid tumors

Question 4

Gemcitabine

Answer 4

S phase specific
MOA: converted to dFdCDP or dFdCTP –> inhibition of ribonucleotide nuclease –> inhibits DNA polymerase
PK: IV only, short half life
ADEs: myelosuppression, N/V, flu-like sx
Other: radiosensitizer***, can be used in solid tumors

Question 5

5-FU

Answer 5

S phase specific
MOA: inhibits TS (fDUMP), interferes with RNA (FUTP), inhibits DNA (fdUTP)
PK: parenteral only, low CNS penetration, short half-life
ADEs: GI (N/V, diarrhea, anorexia, ulcers), myelosuppression, dermatitis, photosensitivity
Other: DPD deficiency can cause toxicity; better efficacy when combined with leucovorin

Question 6

Capecitabine

Answer 6

S phase specific
MOA: inhibits TS (fDUMP), interferes with RNA (FUTP), inhibits DNA (fdUTP)
PK: good PO BA
Other: given as 2 week PO regimen

Question 7

MTX

Answer 7

S phase specific
MOA: DHFR inhibitor –> inhibition of de novo synthesis
- more selective for DHFR vs naturally occuring dihydrofolate
PK: doses <25mg/m2 good PO BA; if over 25mg/m2 must be given parenterally; triphasic elimination; renal elimination, requires renal dosing
ADEs: myelosuppression, GI, alopecia, nephrotoxic, hepatotoxic, defective spermatogenesis, abortion, teratogenic
DI: ASA, NSAIDs, penicillin, cephalosporin (decrease excretion)
Rescue agent: leucovorin; does NOT reverse neurotoxicity

Question 8

Polyglutamated MTX

Answer 8

retained longer w/i cancer cells

higher risk of ADEs but also higher efficacy

Question 9

Pemetrexed

Answer 9

MTX that specifically targets TS

higher risk of erythematous and pruritic rash

Question 10

Leucovorin

Answer 10

Rescue agent for MTX
MOA: unknown, but can only save cells that are not lethally damaged; gains access to cells via PGMTX
- must be given 24-36 hours after start of HDMTX
- HDMTX: >500mg/m2
*L-enantiomer is more potent

Question 11

Irinotecan

Answer 11

G2 phase specific
MOA: Topo 1 inhibitor
PK: converted to active form (SN-38) in liver; biliary excretion; SN-38 t1/2 = 11.5 hours
ADEs: diiiiiiiiiarrhea, myelosuppression
Other: diarrhea w/i 24 hrs is d/t high ACh: tx w atropine, diarrhea after 24 hours should be treated w loperamide

Question 12

Etoposide

Teniposide

Answer 12

G2 phase specific
MOA: Topo 2 inhibitor –> prevents resealing of DNA
ADEs: myelosuppression, N/V/D, stomatitis, hypotension with fast infusion
Other: etoposide-induced leukemia with cummulative doses >2000mg/m2

Question 13

Bleomycin

Answer 13

G2 phase specific
MOA: forms iron complexes that generate free radicals on DNA –> DNA breakage
PK: large molecule, low CNS penetration; degraded by hydrolases found in tissues (no cyps!)
ADEs: pulmonary toxicities (cumm. doses >250mg), cutaneous toxicities, minimal myelosuppression
Other: intralesional bleomycin used for warts

Question 14

Vincristine

Answer 14

M phase specific; Vinca alkaloid
MOA: binds beta tubulin and inhibits polymerization with alpha tubulin to inhibit microtubule formation
PK: metabolized by CYPs, t1/2 = 20 hrs
ADEs: neurotoxicity (d/t high affinity for axonal microtubules), constipation, alopecia
NEVER GIVE VINCA ALKALOIDS INTRATHECALLY

Question 15

Vinblastine

Answer 15

M phase specific; Vinca alkaloid
MOA: binds beta tubulin and prevent interaction with alpha tubulin to inhibit polymerization
PK: CYPs, t1/2 = 23 hrs
ADEs: Myelosuppression, N/V, alopecia, SIADH
NEVER GIVE INTRATHECALLY

Question 16

Vinorelbine

Answer 16

M phase specific; Vinca alkaloid
MOA: binds beta tubulin and prevent interaction with alpha tubulin to inhibit polymerizatio
PK: CYPs, t1/2 24 hrs
ADEs: granulocytopenia, thrombocytopenia, neutoxicity
Other: may cause allergic rxn or mild, reversible change in liver enzymes

Question 17

Paclitaxel

Answer 17

M phase specific; Taxane
MOA: bind inner surface of beta tubulin and inhibit depolymerization
PK: minimal absortion so given with ethanol and castor oil, CYP metabolism, t1/2 10-14 hrs
ADEs: myelosuppression, myalgias, neuropathy, hypersensitivity that can be reduced with premeds
Other: non-linear PK

**albumin-bound nanoparticle is water soluble and not associated with hypersensitivity & myelosuppression

Question 18

Docetaxel

Answer 18

M phase specific; Taxane
MOA: bind inner surface of beta tubulin and inhibit depolymerization
PK: better solubility but still formulated with polysorbate 80 to increase absorption; t 1/2 12 hrs
ADEs: neutropenia, pneumonitis, respiratory failure
Other: less peripheral neuropathy and hypersensitivity